Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response

Objective: infrarenal aortic cross-clamp-induced lower torso ischaemia-repe rfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of th is study was to investigate whether manipulation of the endogenous renal ni tric oxide response can ameliorate subsequent renal injury. Methods: groups of male Wistar rats (n = 6) were treated with one of the fo llowing agents before being subjected to 60 min of infrarenal aortic cross- clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered a fter a left nephrectomy. The glomerular filtration rate (GFR) of the remain ing kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury. Results: animals treated with L-NMMA prior to aortic cross-clamping had a s ignificantly impaired GFR compared to controls on the second (p<0.01, Mann- Whitney U-test) and seventh (p<0.05, Mann-Whitney U-test) postoperative day . Hydrocortisone and 1400W had no significant effect on GFR on the second o r seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seven th postoperative day. Conclusions: these results show that the endogenous nitric oxide response p rotects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients under going aortic aneurysm repair by preventing acute renal failure.